von Willebrand's disease (vWd) is an inherited coagulation disorder characterized by a dificiency of factor VIII clotting activity, VIII antigen (VIIIag), and restocetin cofactor activity. von Willebrand's disease antigen II (vWagII) is a new plasma and platelet protein identified by this investigator as being deficient in the plasma and platelets of patients with von Willebrand's disease. It is immunologically distinct from VIIIag. The study will further purify and characterize vWagII as well as develop a sensitive assay for its detection. The role of vWagII in coagulation function, platelet aggregation, as well as endothelial cell-platelet interaction will be studied. vWAGII can be purified more than 2000-fold by heat defibrination of commercail factor VIII concentrates and molecular exclusion chromatography in 4% agarose. Further purification will be achieved through combining these schemes with affinity chromatography, immune absorption, and isoelectric focusing. Once hemogeneous purification is achieved, molecular weight, carbohydrate content, as well as subunit composition will be ascertained. Immunopurified antibody will be labeled with 125I. Autoradiography with the Laurell method will be used to quantitate vWagII in plasma and platelets. Coagulation tests will evaluate the interaction of vWagII with the coagulation system and platelet function. vWagII will be localized within the platelet and endothelial cell by physical and immunologic techniques. Clinical studies have shown that the hemorrhagic tendency of individuals with vWd is not entirely corrected by replacement with factor VIII concentrates and individuals are left with a prolonged bleeding time. The identification of a second plasma and platelet protein deficient in vWd may play a role in explaining this phenomenon.